psychologywikiaorg-20200213-history
Genetic counseling: Hereditary Nonpolyposis Colorectal Cancer (HNPCC)
' Lynch Syndrome / ' Hereditary Nonpolyposis Colorectal Cancer (HNPCC) 'Contracting' *'Introductions' *'What are your main concerns? What do you hope to learn today?' *'What do you know about colon cancer?' 'Review Family and Medical History' *'Medical History' **'How have you gotten to this point?' **'Screening practices?' **'Other significant illnesses, hospitalizations?' *'Family History' **'Other individuals with any type of cancer?' **'If affected:' ***'Age and date at diagnosis, death' ***'Current age' ***'Type, location, stage of primary cancer' ***'Secondary cancer - metastasis or new primary' ***'Environmental exposures' **'If unaffected:' ***'Current age' ***'Health and history of illness' ***'If deceased, cause and age at death' **'Screening practices' **'Family thoughts on cause of cancer?' 'Colon Cancer' *'Third leading cause of cancer in men and women' **'9% of new cancer diagnoses, 11% of all cancer deaths' **'Incidence is over 160,000 new cases of colon and rectal cancer per year' **'About 5-10% of all colorectal cancers are hereditary' ***'3-7% due to Lynch Syndrome / HNPCC' ***'1% due to FAP' **'About 10-30% of colorectal cancers are familial' **'Average diagnosis is age 44' *'Caused by uncontrolled proliferation of cells in colon or rectum' **'Symptoms may include blood in stool, diarrhea, constipation, reflux, stomach cramps, frequent bloating, weight loss, or unusual and continuing lack of energy' **'Cancer cells may enter blood or lymphatic system and metastasize to form secondary tumors in other parts of body' *'Multifactorial disorder involving both genetic and non-genetic factors' **'Non-genetic factors' ***'Diet: high fat, low fiber, high red meat intake, not enough fresh foods, processed foods' ***'Colorectal polyps (adenomatous polyps)' ***'Alcohol, cigarettes' ***'Chronic disease of bowel (Crohn's disease, inflammatory bowel disease, ulcerative colitis)' ***'Obesity' **'Genetic factors' ***'Hereditary colorectal cancer syndromes' ****'HNPCC and FAP' ****'Rare colorectal syndromes: Peutz-Jeghers Syndrome, Juvenile Polyposis Coli' *'Lynch Syndrome Cancers' **'Colon Cancer' **'Endometrial Cancer' *'Lynch Syndrome Cancers' **'Colon Cancer' **'Endometrial Cancer' *'Ovarian Cancer' *'Gastric Cancers' *'Hepatobiliary Cancers' *'Renal Pelvic Cancer' *'Pancreatic Cancer' *'Skin Cancers (Muir Torre)' *'Brain Cancer' 'Genetic Etiology of Hereditary Colon Cancer' *'Autosomal dominant inheritance' **'Each child of mutation carrier has 50% chance of inheriting mutation' **'Mutations in DNA mismatch repair genes' ***'MSH2 at 2p22' ***'MLH1 at 3p21' ***'PMS1 at 2q31' ***'PMS2 at 7p22' ***'MSH6 at 2p16' ***'Other more rare genes' ***'60% of HNPCC due to mutations in MSH2 or MLH1' **'Carcinogenesis due to loss of heterozygosity of one of genes above' ***'Causes defective mismatch repair' ***'Mutations accumulate throughout the genome' **'Microsatellite instability (MSI)' ***'Provides indirect evidence for presence or absence of germline mutation' ***'Due to genome wide instability of replication and repair of repeat sequences' ***'10-15% of sporadic tumors show MSI, >95% of HNPCC tumors show MSI' *'Penetrance variable - use lifetime cancer risks for mutation carriers' **'Mutation also increases risk for other types of cancer besides colorectal cancer' **'30% risk of second primary 10 years after original diagnosis' **'50% risk of second primary 15 years after original diagnosis' 'Cancer Risk Assessment' *'Features of hereditary colorectal cancer' **'More than one generation affected' **'Early age at diagnosis' **'Bilateral or multiple primary cancers' **'Combination of tumors consistent with specific cancer syndrome' *'Strengths and limitations of cancer risk assessment' **'Knowledge of family history may be limited' **'Cancer occurs with or without hereditary cancer syndrome' **'Can't diagnose on the basis of family history information alone' *'Features associated with HNPCC' **'Polyps present in small numbers or not at all' **'Proximal (right-sided) colon cancer' **'Mean age at diagnosis is 45 years' *'Individual risk based on personal/family history: ________' *'Muir-Torre Syndrome' **'Variant of HNPCC' **'Associated with MSH2 or MLH1 mutations' **'Typical features of HNPCC' **'Also includes sebaceous gland tumors and keratoacanthomas' *'Turcot Syndrome' **'Rare hereditary syndrome of multiple colorectal adenomas and brain tumors' **'Two subtypes' ***'APC mutations associated with medulloblastomas' ***'MMR mutations associated with glioblastomas' 'Genetic Testing' *'Diagnostic/Testing Criteria for HNPCC' **'Amsterdam Criteria' ***'Family must meet ALL of the following' ****'Three cases of colorectal cancer' ****'One affected person is first-degree relative of other two' ****'Two successive generations affected' ****'One diagnosis < 40 years' ****'FAP excluded in cases of colon cancer' ****'Tumors verified by pathology' ***'Failure to meet these criteria DOES NOT exclude HNPCC' **'Modified Amsterdam Criteria' ***'Family must meet ALL of the following' ****'Three relatives with HNPCC-related cancer' ****'One person is first-degree relative of other two' ****'Two successive generations affected' ****'One diagnosis < 50 years' ****'FAP excluded in cases of colon cancer' ****'Tumors verified by pathology' ***'HNPCC-related cancers include colorectal, endometrial, small bowel, ureter, renal pelvis)' **'Bethesda Guidelines for eligibility for MSI testing' ***'Family or proband meets at least one criteria' ****'Family fits either Amsterdam criteria' ****'Proband has two HNPCC-related cancers' ****'Proband has CRC plus 1st degree relative with HNPCC-related cancer or CRC adenoma <45 years' ****'Colorectal or endometrial cancer diagnosed before 45 years' ****'Right-sided colon cancer if undifferentiated diagnosed before 45 years' ****'Signet-ring cell type colorectal diagnosed before 45 years' ****'Colon adenomas diagnosed before 45 years' ***'If high MSI, proceed to germline mutation testing' ***'Bethesda Revised Guidelines' ***'1. The patient is younger than age 50.' 2. The patient has multiple HNPCC-associated tumors in the colon or in other areas known to be caused by the same mutations, either at the same time or occurring over a period of time. 3. A patient younger than age 60 has colorectal cancer that has microscopic characteristics that are often indicative of MSI. 4. A patient has one or more first-degree relatives who had an HNPCC-related tumor at age 50 or younger. 5. A patient has two or more first- or second-degree relatives who had HNPCC-related tumors at any age. *'Common adult cancers may be due to one of several genes or genetic and environmental interactions' **'Negative result difficult to interpret since it can be more than one gene' **'Preferable to identify mutation in relative with cancer before testing other at-risk relatives' **'General population screening not appropriate for this reason' **'DNA banking is option to defer testing until sometime in future' *'Testing procedures' **'Process' ***'Blood drawn here and sent to outside lab (Myriad)' ***'Results usually take about 4 weeks' **'Payment methods' ***'Patient pay with check, money order, credit card' ***'Insurance claims' ****'Submit patient insurance authorization with sample' ****'Requires 20% copay or insurance verified patient portion' ***'Medicare claims - Medicare Waiver of Liability required' ***'Institutional pay - Myriad bills institution directly' **'Current prices' ***'Comprehensive COLARIS (MLH1 and MSH2 sequencing) $1950' ***'Single Site COLARIS (known family mutation) $315' ***'Micorsatellite Instabilty $600' ****'Used to screen before DNA testing' ****'Must be done on tumor tissue' ****'Cannot be billed to insurance' **'Practice guidelines for testing' ***'If positive for Bethesda criteria, start with MSI' ***'If MSI high, consider genetic testing' ***'If MSI low or negative, consider testing if Amsterdam positive' ***'If Bethesda and Amsterdam negative, manage based on family history' *'Mutation identified' **'Increased risk for cancer' **'Gene could be passed on to children' **'Other at-risk relatives should be informed and offered counseling' **'Important to establish management plan' **'Insurance issues' *'Mutation not identified' **'Inherited cancer can't be ruled out since mutation may have been missed or exist in another gene' **'May be no genetic explanation for cancer in family' **'Person with cancer who does not have mutation may be sporadic case' **'Relatives may still be at risk and should discuss family history with their doctor' *'Limitations of testing' **'Can't predict when a person with a mutation will develop cancer' **'Not all persons with mutation will develop cancer' **'Some mutations may be missed or can't be interpreted' **'Efficacy of screening for some related cancers (eg ovarian) is unknown' *'Benefits of testing' **'May provide information' ***'Explanation for cancer in family' ***'Increased surveillance or plan for future' ***'Clarify risks to children and other family members' **'Reassurance' **'Colon surveillance in at risk persons proven to reduce mortality' *'Risks of testing' **'Insurability' **'Employment issues' **'Confidentiality' **'May alter family relationships' **'Adverse psychological effects' ***'Survivor guilt' ***'Transmitter guilt' ***'Depression' ***'Anxiety' *'Not appropriate to offer testing for adult onset disorders for prenatal diagnosis or to anyone under age 18' 'Screening and Management Options' *'Screening guidelines' **'Colonoscopy' ***'Starting at age 25 or 10 years before age of first colorectal cancer diagnosis' ***'Repeat annually' ***'Surveillance decreases mortality by 65%, decreases CRC by 62%' ***'Promotes early detection, improved survival' **'Endometrial and ovarian cancer' ***'Transvaginal ultrasound, CA-125 levels starting at age 25 annually or ten years prior to the youngest age of afflicted family member, whichever comes first.' ***'Endometrial biopsy annually starting at age 25 or ten years prior to the youngest age of afflicted family member whichever comes first.' **'Stomach' ***'If previous family member affected' ***'Upper GI endoscopy every 1-2 years starting at age 25 or ten years prior to the youngest age of afflicted family member whichever comes first.' **'Urinary tract' ***'If previous family member affected' ***'Ultrasound and urine cytology every 1-2 years starting at age 25 or ten years prior to the youngest age of afflicted family member.' ***'Annual Examination of Skin for cancerous growths' *'Prophylactic surgery' *'Subtotal colectomy if cancers are discovered' *'Hysterectomy with oophorectomy following child bearing years' ' ' ' ' *'Chemoprevention' *'Current multicenter trial recruiting patients with known mutation or high MSI tumors and Amsterdam positive family history' *'Current trial occuring in the UK' *'Not known if chemopreventative therapies are effective for those with Lynch syndrome however prophylactic chemotherapy is prescribed at Stage II and above.' 'Psychosocial Issues' *'Motivation for undergoing testing' **'Decision-making about testing, surveillance, and prevention' **'Protect lives' **'Stress level, previous experiences with cancer either within self or other family members' **'Protection of family members' **'Hope and enhanced longevity' ' ' *'Reactions to positive, negative, and uninformative results' **'Changes in medical management' **'Initial feeling of being overwhelmed' **'Feelings of relief and/or resolution' **'Notification to family members in order to protect them' *'Family, social support system' 'Resources' ' ' *'American Cancer Society' :National Headquarters :1599 Clifton Road, N.E. :Atlanta, GA 30329 :(800) ACS-2345 :' ' *'Hereditary Colorectal Cancer Registry' :The Johns Hopkins Hospital :550 North Broadway, Suite 108 :Baltimore, MD 21205-2011 :(410) 955-3875 :' ' :*'Lynch Syndrome International' :P.O. Box 5456 :Vacaville, California :707-689-5089 'References' *'Everett, J. "Hereditary Non-Polyposis Colorectal Cancer." Genetic Counseling and Cancer lecture (2002).' *'"Identifying and Managing Risk for Hereditary Nonpolyposis Colorectal Cancer and Endometrial Cancer (HNPCC)." American Medical Association (2001).' *'"Module 6: Hereditary Colorectal Cancer Syndromes." OncoSep 43-55.' *'"The Johns Hopkins Guide for Patients and Families: Hereditary Nonpolyposis Colorectal Cancer." The Johns Hopkins University (1995).' 'Notes' The information in this outline was last updated in 2002. ' ' This material has been imported fom the wikibook "Genetic counseling"[ 'http://en.wikibooks.org/wiki/Genetic_counseling] under the GNU Free Documentation License. '